This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The goals of this study are to demonstrate and confirm the role of genetic factors in the development of chronic otitis media with effusion and recurrent otitis media (COME/ROM) to improve understanding of its underlying biological and pathological mechanisms. This will enable development of more effective prevention and treatment strategies,including targeting high risk children for rigorous surveillance and developing prevention and aggressive treatment strategies to prevent COME/ROM and its sequelae. This is the continuation of an initial funding period during which pedigree ascertainment, recruitment, and extensive phenotypic assessment was completed, and a genome scan performed. Regions of the genome were identified that contain quantitative trait loci (QTLs) contributing to risk of COME/ROM, and candidate gene analyses revealed an association between polymorphisms in FBXO11, the human homolog of the Jeff mouse model gene, and COME/ROM. During the current period, we are performing targeted linkage studies on chromosomes 10, 19 and 3 identified in the genome scan of the family collection. Results of the fine mapping will be used to identify a linkage peak for detailed molecular genetic analysis. We will also continue to recruit unrelated, well characterized cases and controls for association studies to compare with family-based analysis and explore a series of candidate genes supporting linkage to COME/ROM in the family collection using focused SNP genotyping and family-based association analysis. COME/ROM susceptibility genes will be identified by performing a detailed analysis of genes and/or haplotype blocks associated with COME/ROM in both families and cases and controls. It is anticipated that this study will provide new insights into the gene-gene and gene-environment interactions that contribute to the development of COME/ROM in childhood.